Inbaraj Baskaran Stephen, Hua Leng-Huei, Chen Bing-Huei
Department of Food Science, Fu Jen Catholic University, New Taipei City 24205, Taiwan.
Department of Nutrition, China Medical University, Taichung 40401, Taiwan.
Pharmaceutics. 2021 Nov 5;13(11):1871. doi: 10.3390/pharmaceutics13111871.
Resveratrol, a phenolic compound possessing vital biological activities such as anti-cancer, is present abundantly in grape skin, a waste produced during the processing of grape juice. The objectives of this study were to prepare resveratrol-gold nanoparticles and a resveratrol nanoemulsion from grape skin and study their inhibition effects on pancreatic cancer cells BxPC-3. The spherical-shaped citrate gold nanoparticles (GNPs) and resveratrol-gold nanoparticles (R-GNPs) were, respectively, prepared with a surface plasmon resonance peak at 528 and 538 nm, mean particle size of 20.8 and 11.9 nm, and zeta-potential at -32.7 and -66.7 mV, by controlling an appropriate concentration of citrate/resveratrol and gold chloride as well as stirring time and temperature. The resveratrol nanoemulsion, composed of soybean oil, Tween 80, and sucrose fatty acid ester in glycerol and water, possessed a high storage stability with a mean particle size of 14.1 nm, zeta-potential of -49.7 mV, and encapsulation efficiency of 95.5%. An antiproliferation study revealed that both R-GNPs and resveratrol nanoemulsion could effectively inhibit the growth of pancreatic cancer cells BxPC-3, with the latter showing a higher inhibition effect. Western blot analysis implied that both can down-regulate expressions of cyclin A, cyclin B, CDK1, and CDK2 and up-regulate expressions of p53 and p21, accompanied by enhancing cytochrome C expression, decreasing BcL-2 expression, increasing Bax expression, and leading to the elevation of caspase-8, caspase-9, and caspase-3 activities for cell apoptosis execution. Future research is needed to study the inhibition of pancreatic tumors in vivo by R-GNPs and resveratrol nanoemulsions.
白藜芦醇是一种具有抗癌等重要生物活性的酚类化合物,大量存在于葡萄皮中,而葡萄皮是葡萄汁加工过程中产生的废弃物。本研究的目的是从葡萄皮中制备白藜芦醇 - 金纳米颗粒和白藜芦醇纳米乳剂,并研究它们对胰腺癌细胞BxPC - 3的抑制作用。通过控制柠檬酸盐/白藜芦醇和氯化金的适当浓度以及搅拌时间和温度,分别制备了球形的柠檬酸盐金纳米颗粒(GNPs)和白藜芦醇 - 金纳米颗粒(R - GNPs),其表面等离子体共振峰分别在528和538 nm,平均粒径分别为20.8和11.9 nm,ζ电位分别为 - 32.7和 - 66.7 mV。由大豆油、吐温80和蔗糖脂肪酸酯在甘油和水中组成的白藜芦醇纳米乳剂具有高储存稳定性,平均粒径为14.1 nm,ζ电位为 - 49.7 mV,包封率为95.5%。抗增殖研究表明,R - GNPs和白藜芦醇纳米乳剂均能有效抑制胰腺癌细胞BxPC - 3的生长,后者显示出更高的抑制效果。蛋白质免疫印迹分析表明,两者均可下调细胞周期蛋白A、细胞周期蛋白B、细胞周期蛋白依赖性激酶1(CDK1)和细胞周期蛋白依赖性激酶2(CDK2)的表达,上调p53和p21的表达,同时增强细胞色素C的表达,降低BcL - 2的表达,增加Bax的表达,并导致半胱天冬酶 - 8、半胱天冬酶 - 9和半胱天冬酶 - 3的活性升高以执行细胞凋亡。未来需要研究R - GNPs和白藜芦醇纳米乳剂在体内对胰腺肿瘤的抑制作用。